Melanin protects the eye from the damaging effects of solar radiation. Genetic diseases such as albinism, which diminish ocular pigmentation, are associated with significant morbidity. The goals of the proposed research are to understand, at the molecular level, the functions of specific gene products involved in the synthesis and packaging of melanin, and the pathogenesis of genetic disorders which affect pigmentation in the eye and skin, resulting in oculocutaneous albinism. The eye is an ideal system in which to address these problems because of the high concentration of melanocytes in ocular tissue and the fact that ocular pigmentation occurs over a predictable postnatal time course. The work proposed will take advantage of the well-studied genetics of eye and coat color in the inbred mouse to address three specific aims: 1. To characterize the product of the pinkeyed-dilution locus with respect to its structure, synthesis, and subcellular distribution. The hypothesis that this protein serves to link the melanosomal membrane to melanin or the melanosomal matrix will be tested. 2. To test the hypothesis that interactions among the proteins encoded at the albino, brown, slaty and pinkeyed-dilution loci are critical in regulating ocular pigmentation. These interactions will be identified and their consequences upon the function and subcellular trafficking of these proteins will be defined. Subcellular fractionation, antipeptide antisera, biochemical separation techniques, assays of enzyme function and chemical analysis of melanin will be utilized to test this hypothesis. 3. To understand the pathogenesis of specific mutations (genetic diseases) which affect these proteins and thus reduce ocular pigmentation. The effects of defined mutations at these loci on the expression, function and subcellular distribution of their respective gene products and those of the other three proteins of interest in ocular melanocytes taken from inbred mice from birth through adulthood will be analyzed.